Interpretation of Test Results

The discovery of an expanded repeat sequence in DM has greatly improved our ability to confirm the diagnosis in symptomatic patients, to detect DM carriers who are asymptomatic or who show few of the classical signs of the disease, and for prenatal testing when a parent has been diagnosed with the disorder. Although closely linked restriction fragment length polymorphism (RFLP) markers were available for several years, linkage analysis is not as accurate as direct DNA testing for the mutation, especially when there is an uncertain diagnosis or when key family members are unavailable for testing. Also, linkage test results provide no information regarding the severity of the disease. Molecular testing has largely replaced muscle biopsy, muscle enzyme study, and elec-tromyography as the first diagnostic procedure.

The triplet repeat size does correlate with muscular disability and is inversely related with the age of onset of the disease. However, there is a significant overlap of repeat size in patients with differing severity. When unrelated affected individuals with small to moderate differences in repeat sizes are compared, accurate prediction of the severity of the disease in each case is generally difficult. However, when a child has a significant increase in allele size compared to the parent, the child will almost certainly become symptomatic at an earlier age of onset and will have more severe disease. Lastly, as a result of the somatic heterogeneity observed in DM, genotype/phenotype associations derived from leukocytes may not be as accurate as the measurement of the repeat size in the affected tissue (muscle, heart, others). CTG expansions may be 2- to 13fold greater in the DNA isolated from skeletal muscle than in the DNA from leukocytes.24

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